Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

Autor(es):Mostrar menos -

Dias Costa, Ericka Francislaine ; Santos, Erika Stocco ; Liutti, Vitor Teixeira ; Leal, Frederico ; Antunes Santos, Vivian Castro ; Rinck-Junior, Jose Augusto ; Viviane Mariano, Fernanda ; Malheiros Coutinho-Camillo, Claudia ; Altemani, Albina ; Passos Lima, Carmen Silvia ; Lourenco, Gustavo Jacob

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY; v. 142, n. 9, p. 1917-1926, SEP 2016.
• Citações Web of Science: 4

Resumo

We examined the influence of OGG1 c.977C > G (rs1052133), APEX1 c.444T > G (rs1130409), XRCC1 c.-77T > C (rs3213245), c.580C > T (rs1799782), c.839G > A (rs25489) and c.1196G > A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis. Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan-Meier estimates and Cox regression analyses. XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T > C, c.580C > T, c.839G > A and c.1196G > A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C > T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02). Our data present, for the first time, evidence that inherited OGG1 c.977C > G; XRCC1 c.-77T > C, c.580C > T, c.839G > A and c.1196G > A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes. (AU)

• Processo FAPESP: 12/18623-1 - Influência de polimorfismos em genes relacionados ao sistema de reparo de DNA na suscetibilidade ao carcinoma de células escamosas de orofaringe
• Beneficiário: Erika Stocco dos Santos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica